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Paper of the Month - April 2025
selected by the BMAS Scientific Board

Subchondral bone marrow adipose tissue lipolysis regulates bone formation in hand osteoarthritis

Mauro Maniglio1 , Léa Loisay 2 , Diego de Haro2 , Alexander Antoniadis3 , Thomas Hügle2 , Jeroen Geurts4
  • Plastic and Hand Surgery, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland; Department of Hand Surgery, Balgrist University Clinic, Zürich, Switzerland.
  • 2 Rheumatology, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland.
  • 3 Orthopaedics, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland.
  • 4 Rheumatology, Department of Musculoskeletal Medicine, University Hospital Lausanne and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland. Electronic address: Jeroen.Geurts@chuv.ch. 
Osteoarthritis and Cartilage 33 (2025) 322–329
PMID: 39725154 | DOI: 10.1016/j.joca.2024.12.005

ABSTRACT

Objective: Bone marrow adipose tissue (BMAT) is emerging as an important regulator of bone formation and energy metabolism. Lipolysis of BMAT releases glycerol and fatty acid substrates that are catabolized by osteoblasts. Here, we investigated whether BMAT lipolysis is involved in subchondral bone formation in hand osteoarthritis (OA).

Methods: Subchondral BMAT lipolysis and bone marrow adipocyte (BMAd) morphology were studied in clinical specimens of carpometacarpal (CMC-1) and distal interphalangeal joint OA. BMAd size, osteoblast numbers and expression of lipolysis enzymes (ATGL, phospho-HSL, MGLL) were compared between regions of low and high bone formation. Free fatty acids, glycerol and bone biomarkers were measured in osteochondral explants.

Results: Subchondral BMAd size was positively correlated with BMI (r = 0.60, [0.082,0.87]) and reduced in regions of high bone formation (-1149 µm2, [-1977,-726.2]). Osteoblast numbers were negatively correlated with BMAd size (r = -0.48, [-0.73,-0.12]). All lipolysis enzymes were expressed in both in BMAds and activated osteoblasts and the area percentages of ATGL (+2.26% [0.19,3.47]), phospho-HSL (+1.57% [0.31,6.48]) and MGLL (+4.04% [1.09,5.69]) were increased in regions of high bone formation. Secreted glycerol levels, but not free fatty acids, were correlated with bone formation markers pro-collagen type I (rho = 0.90) and alkaline phosphatase (rho = 0.78).

Conclusion: Our findings reveal a previously unrecognized role of BMAT lipolysis in regulating bone formation in hand OA, which may be modulated by BMI.

Keywords: Bone; Bone marrow adipose tissue; Hand OA; Lipolysis; Osteoblast.

Figure 2. Reduction of BMAd size in areas of high remodeling.

A panel of histology images and graphs demonstrating Reduction of BMAd size in areas of high remodeling.

Fig. 2: Typical morphology of subchondral bone and BMAT in low and high remodeling areas visualized by whole-mount Oil red-O and Hoechst staining. Scale bar = 200 μm. (A) Typical morphology of subchondral BMAT in areas of low and high remodeling visualized by Safranin-O staining. Osteoblasts indicated by red arrowheads. Scale bars = 500 μm (low magnification) and 100 μm (high magnification). (B) Median BMAd size quantified from high magnification images. P-value < 0.0005 by Wilcoxon matched-pairs signed rank test, (n = 13) (C) Osteoblast numbers quantified from high magnification images. P-value < 0.001 by paired t-test, (n = 13) (D). Scatterplot showing correlation between median BMAd size and osteoblast numbers in low and high remodeling areas of thirteen CMC-1 joints and the regression line with 95% confidence intervals. (E).

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